Intraluminal device with controlled biodegradation

ABSTRACT

An intraluminal device with controlled biodegradation is provided. The intraluminal device comprises a biodegradable tubular main body. An outer photodegradable layer is disposed over at least a portion of the intraluminal device. The photodegradable outer layer is chemically inert to the body fluids of the implanted region, thereby preventing premature biodegradation of the stent. Degradation of the outer photodegradable layer after a predetermined time occurs by irradiating the layer with UV light waves. After removal of the outer photodegradable layer, the tubular main body becomes exposed to its in vivo environment, thereby allowing biodegradation of the tubular main body.

BACKGROUND

The present disclosure relates to a biodegradable intraluminal device,such as an intraluminal stent, that undergoes biodegradation within abody lumen. Biodegradable devices such as intraluminal stents arecurrently implanted in various body lumens of a patient, including thecoronary vasculature, the tracheal tract, and the gastrointestinaltract. In certain situations, it may be desirable for the stent to bebiodegradable or bioabsorbable so as to reduce the adverse risks thatwould otherwise be associated with the stent's continued presence onceits usefulness at the treatment site has ceased or has at least becomesubstantially diminished. To such end, some stents have heretofore beenwholly constructed of materials that are biodegradable or bioabsorbable.It is desirable to select a material that while biodegradable isnonetheless biocompatible and has sufficient strength to support theloads a particular stent is to be subjected to when implanted.

When the stent is implanted within the target body region, the inner andouter surfaces of the biodegradable stent contact bodily fluids whichcause the onset of biodegradation of the implanted stent. As the stentbiodegrades in vivo, the stent loses mass. Oftentimes, the rate of massloss can be significant and becomes difficult to regulate and control.The significant loss in mass can lead to a premature loss in mechanicalstrength of the stent, thereby rendering the stent incapable ofmaintaining the patency of the target body lumen for its intended timeframe.

SUMMARY

In a first aspect, a hybrid degradable stent is provided. The hybridstent comprises a generally tubular main body comprising an innerdiameter and an outer diameter. The tubular body is formed from abiodegradable material. The hybrid stent further comprises aphotodegradable layer disposed over at least a portion of the innerdiameter and/or the outer diameter of the biodegradable tubular body.The layer is formed from a photodegradable material that is chemicallyinert to bodily fluids contained at an implanted site. Thephotodegradable layer is selectively adapted to be activated from achemically inert state to a photodegradable state. The photodegradablestate initiates degradation of the photodegradable layer so as to exposeat least a portion of the biodegradable material to begin biodegradationof the biodegradable material.

In a second aspect, a degradable stent kit is provided. The kitcomprises a generally biodegradable tubular body comprising a proximalend and a distal end, and a lumen extending from the proximal end to thedistal end. The body further comprises a photodegradable materialdisposed over at least a portion of the biodegradable tubular body. Thephotodegradable material is chemically inert when deployed into a bodylumen of a patient. The kit also includes a light-irradiating systemconfigured to activate the photodegradable material from the chemicallyinert state to a photodegradable state. The light-irradiating systemcomprises a light source and a fiber section. The fiber sectioncomprises a proximal section in communication with the light source anda distal section in communication with the tubular body. The fibersection is adapted to propagate UV light from the proximal section tothe distal section and thereafter irradiate UV light from the distalsection to the photodegradable material.

In a third aspect, a method for controllably degrading a stent within abody lumen of a patient is provided. A generally tubular body isprovided. The tubular body is formed from a biodegradable material. Thebody is characterized by an inner diameter and an outer diameter. Thebody further comprises a photodegradable layer disposed over at least aportion of the inner and/or the outer diameters of the biodegradabletubular body. The tubular body is deployed into the body lumen. Anelongated light-irradiating conductor is advanced towards the deployedtubular body. A specific wavelength of light is irradiated along theconductor and towards the photodegradable layer of the stent. Thephotodegradable layer is activated from a chemically inert state to aphotodegradable state. At least a portion of the photodegradable layeris photodegraded.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 a shows a cross-sectional view of a hybrid biodegradable stenthaving an outer photodegradative layer and an inner photodegradativelayer over the biodegradable stent;

FIG. 1 b shows a perspective view of the hybrid biodegradable stent ofFIG. 1 a;

FIG. 2 a shows a partial cross-sectional view of an optical fiberinserted within a luminal space of the hybrid biodegradable stent ofFIG. 1 a, the optical fiber propagating ultraviolet light towards theinner photodegradative layer so as to activate and begin the degradationprocess of the inner photodegradative layer;

FIG. 2 b shows a partial cross-sectional view of the optical fiberinserted within the luminal space of the hybrid biodegradable stent ofFIG. 1 in which a portion of the inner photodegradable layer has beenactivated, degraded, and removed with the optical fiber continuing topropagate ultraviolet light towards the inner photodegradative layer soas to activate, degrade, and remove a further portion of the innerphotodegradative layer;

FIG. 2 c shows a partial cross-sectional view of the optical fiberinserted within the luminal space of the hybrid biodegradable stent ofFIG. 1 a in which all of the inner photodegradative layer has beenremoved within the inner surfaces of the biodegradable stent;

FIG. 3 a shows a partial cross-sectional view of the optical fiber nowpositioned outside of luminal space of biodegradable stent along aproximal edge of stent, the optical fiber propagating ultraviolet lighttowards the outer photodegradative layer so as to initiative activationand begin degradation of the outer photodegradative layer along theouter surface of the biodegradable stent;

FIG. 3 b shows a partial cross-sectional view of the optical fiberpositioned outside of luminal space of biodegradable stent and slightlyadvanced distally along an outer surface of stent in which a portion ofthe outer photodegradable layer has been activated, degraded, andremoved with the optical fiber continuing to propagate ultraviolet lighttowards the outer photodegradative layer so as to further activate,degrade, and remove the outer photodegradative layer along the outersurfaces of the biodegradable stent;

FIG. 3 c shows a partial cross-sectional view of the optical fiberoutside of luminal space of biodegradable stent and advanced furtherdistally along the outer surface of the stent so as to photodegrade andremove all of the outer photodegradative layer from the outer surfacesof the biodegradable stent;

FIG. 4 a shows a lens affixed to the distal end of the optical fiber,the lens redirecting the UV waves in a first direction normal to thelongitudinal axis of the optical fiber; and

FIG. 4 b shows the optical fiber rotated so as to reconfigure the lenssuch that the UV waves are redirected in a second direction normal tothe longitudinal axis of the optical fiber.

DETAILED DESCRIPTION

The relationship and functioning of the various elements of thisinvention are better understood by the following detailed description.However, the embodiments of this invention as described below are by wayof example only. It should also be understood that the drawings are notto scale and in certain instances details, which are not necessary foran understanding of the present invention, have been omitted such asconventional details of fabrication and assembly. Unless otherwisespecified, all percentages expressed herein are weight percentages basedon the whole mixture.

The term “biodegradable” material refers to a material that dissipatesupon implantation within a body, independent of the mechanisms by whichdissipation can occur, such as dissolution, degradation, absorption andexcretion. The actual choice of which type of materials to use mayreadily be made by one of ordinary skill in the art. Such materials areoften referred to by different terms in the art, such as“bioresorbable,” “bioabsorbable,” or “biodegradable,” depending upon themechanism by which the material dissipates. The prefix “bio” indicatesthat the erosion occurs under physiological conditions, as opposed toother erosion processes, caused for example, by high temperature, strongacids or bases, or ultraviolet (“UV”) light.

The terms “proximal” and “distal” as used herein are intended to have areference point relative to the user. Specifically, throughout thespecification, the terms “distal” and “distally” shall denote aposition, direction, or orientation that is generally away from theuser, and the terms “proximal” and “proximally” shall denote a position,direction, or orientation that is generally towards the user.

FIGS. 1A and 1B show a cross-sectional view of an exemplary hybriddegradable stent 100. The hybrid degradable stent 100 comprises abiodegradable stent 101, which is the tubular main body, disposedbetween an outer photodegradable layer 102 and an inner photodegradablelayer 103. FIG. 1A shows that the tubular main body is characterized ashaving an inner diameter “ID” and an outer diameter “OD”. The innerphotodegradable layer 103 extends along the “ID” at an inner surface 110of stent 101. The outer photodegradable layer 102 extends along the “OD”at an outer surface 111 of stent 101. The inner photodegradable surface103 preferably extends along the entire longitudinal length of the stent101 over inner surface 110. Similarly, the outer photodegradable layer102 preferably extends along the entire longitudinal length of the stent101 over outer surface 111. As used herein, the term “layer” refers toany means by which material may be disposed along an inner surface 110and/or an outer surface 111 of the biodegradable stent 101. The innerand the outer photodegradable layers 103 and 102 are chemically inertwhen in contact with bodily fluids at the implanted site. In otherwords, the photodegradable layers are not susceptible to any type ofbiodegradation breakdown that typically occurs when biodegradablematerials are exposed to bodily fluids at the implanted site.Preferably, the inner and the outer photodegradable layers 103 and 102are nonporous and extend along an entire longitudinal length of thestent 101. Accordingly, the inner and the outer photodegradable layers103 and 102 serve as a protective outer covering or sheath over thebiodegradable stent 101 when implanted. When patency of the target bodylumen by stent 100 is no longer required, degradation of the protectivephotodegradable layers 102 and 103 can begin. UV light or another typeof activation agent contacts the photodegradable layers 102 and 103,which causes the photodegradable layers 102 and 103 to become activatedand thereafter degrade. As the inner photodegradable layer 103 and theouter photodegradable layer 102 degrade, they detach from biodegradablestent 101 thereby causing at least a portion of the inner surface 110and outer surface 111 of the biodegradable stent 101 to be exposed.Exposure of outer surface 111 to the implanted environment beginsbiodegradation of the stent 100 along the outer surface 111. Similarly,exposure of inner surface 110 to the implanted environment beginsbiodegradation of the stent 100 along the inner surface 120.Accordingly, the biodegradation of stent 101 can be delayed for apredetermined length of time by maintaining protective photodegradablelayers 102 and 103 on biodegradable stent 101, thereby avoidingpremature biodegradation of biodegradable stent 101.

A variety of photodegradable materials may be used. For example, thephotodegradable layer may be a blend of polymers, which includes a baseor synthetic polymer and small amount of UV photodegradable ketocarbonylcontaining polymer. The amount of keto carbonyl groups in thecomposition may range from about 0.01 wt % to about 5 wt %, based uponthe total weight of the base polymer. The keto carbonyl group is aketone functional group characterized by a carbonyl group (O═C) linkedto two other carbon atoms. The keto carbonyl group can be generallydesignated as R₁(CO)R₂.

The base or synthetic polymer may comprise a vinylidene monomer which iscompatible with the keto carbonyl groups. “Compatible” as used hereinrefers to polymers which can be blended together in the desiredproportions to give a polymer blend of reasonable strength andtoughness. The vinylidene monomer may comprise ethylene, styrene, methylacrylate, methyl methacrylate, vinyl acetate, methacrylonitrile,acrylonitrile, vinyl chloride, acrylic acid, methacrylic acid,chlorostyrene, alpha-methylstyrene, vinyl toluene or butadiene. In oneexample, a blend of polyethylene and about 9.5 wt % methylenemethylisopropenyl ketone copolymer may be utilized. The polyethylene may below density or high density. In another example, a copolymer of 95 wt %styrene and 5 wt % methylisopenylketone may be utilized.

The polymeric composition may also include a condensation copolymer andat least one ketone copolymer in which the amount of the ketonecopolymer ranges from about 0.01 wt % to about 5 wt %. The condensationcopolymer may comprise polyamides, polyesters, polyurethanes,polyethers, polyeopxides, polyamide esters, polyimides,poly(amide-imides), polyureas, and polyamino-acids.

It is preferred to choose an addition copolymer of a similar vinylidenemonomer and an unsaturated ketone, in minor proportion. It is especiallypreferred to use a minor proportion of a UV photodegradable copolymerbased upon one of the monomers of a synthetic polymer. For example,among the especially preferred embodiments are such compositions asblends of polystyrene (major proportion) and keto-carbonyl containingcopolymers of styrene (minor proportion), blends ofpolymethylmethacrylate (major proportion) and keto-carbonyl containingcopolymers of methyl-methacrylate (minor proportion), blends ofpolymethylacrylate (major proportion) and keto-carbonyl containingcopolymers of methylacrylate (minor proportion), and blends ofpolyethylene (major proportion) and keto carbonyl containingethylene-unsaturated ketone copolymers (minor proportion), beingmacro-molecular. The amount of keto carbonyl groups in the compositionmay range from about 0.01 wt % to about 5 wt %.

The keto copolymers used in minor proportion in the preferredcompositions of the present invention are themselves photodegradable onexposure to UV radiation. They may contain from about 0.01-10 wt %,preferably from about 0.01-5 wt %, and most preferably from about 0.02-2wt % of a ketone carbonyl group. They are compatible with the basepolymer (i.e., the synthetic polymer) with which they are to be blended.In the case of addition keto copolymers, the keto groups are located ina side chain at a position immediately adjacent to the backbonepolymeric chain. In the case of condensation keto copolymers, the ketogroups may be located either in a side chain as mentioned above, or inthe polymer backbone. The keto copolymer is blended with the syntheticpolymer so as to give a polymeric composition preferably containing notmore than 3 wt % keto groups in these preferred compositions.

A preferred means for activating degradation of outer photodegradablelayer 102 and inner photodegradable layer 103 is by a light irradiatingsystem 270 (FIG. 2). Referring to FIG. 2, the light irradiating system270 comprises a UV light source 271 and an optical fiber section 203.The intensity 273 or power of the UV light 225 emitted into proximalregion 201 of the optical fiber 203 may be regulated by UV irradiationsystem 270. UV light is delivered from the UV light source 271 throughoptical fiber 203. The optical fiber 203 is constructed to enabletransmission of the high-energy UV light with minimal attenuation of itsintensity 273. Specifically, the proximal region 201 of optical fiber203 is preferably encased in a jacketing material known in the art(e.g., fused silica) to allow propagation of the UV light wavestherethough without significant attenuation or leakage. The distalregion 202 of the optical fiber 203 constitutes the light transmissionsection along which the UV light waves 225 are emitted towards the innerphotodegradable layer 103. The distal region 202 extends towards theinner photodegradable layer 103 (FIGS. 2 a-2 c). FIG. 2 a shows that theproximal region 201 of optical fiber 203 is coupled to the UV lightsource 271 of a suitable wavelength to interact with the innerphotodegradable material of layer 103. The radiation source 271 caninclude an intensity control 273 to regulate the amount of UV light tobe delivered to the optical fiber 203. The UV source 271 can alsoinclude a wavelength tuning or selection control 272 for selectingradiation of a suitable wavelength to interact with the photodegradablematerial of the outer layer 102 and the inner layer 103.

After the hybrid stent 100 has maintained the patency of a body lumen250 for the desired time frame, biodegradation of the stent 101 mayensue, which involves degrading the protective inner photodegradativelayer 103 and the protective outer photodegradative layer 102. FIGS.2A-2C and 3A-3C show the sequence of steps involved in activating,degrading and removing the photodegradable layers 103 and 102 from theinner surface 110 and subsequently the outer surface 111 of stent 101 ata target site within body lumen 250.

Accordingly, FIGS. 2 a-2 c show the optical fiber 203 positioned withinthe lumen 104 of the stent 100 body. Navigating the optical fiber 203 tothe stent 100 may be facilitated by insertion through a sheath orovertube (not shown). Upon the optical fiber 203 reaching the targetsite of body lumen 250, at least the distal region 202 of the opticalfiber 203 may be withdrawn from the sheath or overtube.

The distal region 202 of the optical fiber 203 is preferably designed todiffuse UV light 225 outwardly towards the inner surface 110 of stent101. FIG. 2 a shows a partial cross-sectional view of the optical fiber203 inserted within a luminal space 104 of the hybrid biodegradablestent 100 of FIG. 1 a. The proximal region 201 of the optical fiber 203extends outside of a patient and is connected to the UV source 271 of UVlight irradiating system 270. A suitable wavelength 272 and intensity273 of UV light 225 is selected from the UV light source 271. The UVlight 225 propagates through proximal portion 201 of the optical fiber203 into distal portion 202 of optical fiber 203. The UV light 225diffuses towards the inner photodegradative layer 103 so as to activateand begin the degradation process of the inner photodegradative layer103.

The distal end of the optical fiber 203 can include a divergent lensshape which can disperse the UV light 225 radially outward from the axisof the optical fiber 203 in all directions towards the innerphotodegradable layer 103. The UV light 225 diffuses in all directionstowards inner photodegradable layer 103 such that the UV irradiance isapproximately uniform along the longitudinal length of the stent 101, asshown in FIGS. 2A-2C. Alternatively, the distal tip of the optical fiber203 may be tapered to diffuse the UV light waves 225 outwardly towardsthe inner photodegradable surface 103. The duration for UV irradiationis sufficient for activation of the inner photodegradable material 103to occur. The duration of the UV light irradiation will depend at leastin part on the particular inner photodegradable material 103 used, theconcentration of the ketocarbonyl groups contained within innerphotodegradable layer 103, and the power or intensity 273 emitted fromUV light irradiation system 270. In one example, the time of UVirradiation is about a minute.

There is a predetermined amount of energy associated with the UV light225 at the predetermined wavelength and intensity. As the UV light 225contacts the inner photodegradable layer 103, this energy is sufficientto activate the inner photodegradable layer 103 such that the onset ofcleavage of the chemical bonds of the polymer chains of the UVphotodegradable layer 103 occurs. The emitted UV light 225 is absorbedby layer 103. The absorption of the UV light 225 results in addedthermal energy which is sufficient to cleave the chemical bonds of thepolymer chains of inner photodegradable layer 103. Preferably, the UVlight 225 raises the temperature of the inner photodegradable layer 103to above its glass transition temperature. The material of layer 103begins to disintegrate and degrades to a point where the innerphotodegradable material 103 becomes detached from the inner surface 110of the stent 101. FIG. 2 b shows that a portion of the innerphotodegradable layer 103 has been activated, degraded, and removed asUV light 225 contacts the inner photodegradable layer 103.

UV light 225 continues to propagate through distal region 202 of theoptical fiber 230 so as to further activate and degrade a portion of theinner photodegradable layer 103, thereby removing an additional portionof layer 103 from inner surface 110. FIG. 2 c shows that all of theinner photodegradable layer 103 has been removed so as to expose innersurface 110 of stent 101 to its implanted environment at the body lumen250. Exposure of the inner surface 110 of stent 101 may enablebiodegradation of stent 101 to now occur.

After the inner photodegradable layer 103 has been removed from innersurface 110 of stent 101, the optical fiber 203 may be re-positionedalong the outer surface 111 of the stent 101 as shown in FIGS. 3A-3C toremove outer photodegradable material 102 along outer surface 111 ofstent 101. The proximal region 201 of the optical fiber 203 extendsoutside of a patient and is connected to the UV source 271 of UV lightirradiating system 270. A suitable wavelength 272 and intensity 273 ofUV light 225 is selected from the UV light source 271. The UV light 225propagates through proximal portion 201 of the optical fiber 203 intodistal portion 202 of optical fiber 203. The UV light 225 is emitted anddiffuses towards the outer photodegradative layer 102 so as to activateand begin the degradation process of the outer photodegradative layer102.

FIG. 3 a also shows that a second optical fiber 303 may be positionedalong the outer surface 111 of the stent 101 in which the second opticalfiber 303 is disposed about 180° relative to the optical fiber 203. Asuitable wavelength 272 and intensity 273 of UV light 226 is selectedfrom the UV light source 271. The UV light 226 propagates throughproximal portion 301 of the optical fiber 303 into distal portion 302 ofoptical fiber 303. The UV light 226 is emitted and diffuses towards theouter photodegradative layer 102 so as to activate and begin thedegradation process of the outer photodegradative layer 102 along thebottom portion of stent 101. Having a second optical fiber 303simultaneously remove material from outer photodegradable layer 102eliminates the need to reposition the optical fiber 203 along the outersurface 111 of stent 101, and therefore may reduce the time needed forirradiating UV light from UV irradiating system 270. FIG. 3 a shows thatUV light 225 emitted and diffused from optical fiber 203 and UV light226 emitted and diffused from optical fiber 303 contact outerphotodegradable layer 102 so as to initiative activation and begindegradation of the outer photodegradative layer 102.

Exposure of the outer photodegradable material 102 to UV light waves 225and 226 may be emitted in all directions, as shown in FIGS. 3 a-3 c.FIG. 3 b shows that a portion of the outer layer 102 has been degradedand removed along the outer surface 111 from the stent 101. As a result,the distal portions 202 and 302 of the optical fibers 203 and 303 may beslightly advanced distally along the outer surface 111 of stent 101(FIGS. 3B and 3C) so as to be in close proximity to that portion of theouter photodegradable layer 102 still affixed to the outer surface 111of stent 101. UV light 225 continues to propagate through optical fiber203 and UV light 226 continues to propagate through optical fiber 303 tofurther activate, degrade, and remove additional amounts of the outerphotodegradative layer 102. Propagation of UV light 225 and 226 to outerlayer 102 preferably continues until all of the outer photodegradablelayer 102 has been removed so as to expose outer surface 111 of stent101 to its implanted environment at the body lumen 250. Exposure of theouter surface 111 of stent 101 may enable biodegradation to occur alongthe outer surface 111 of stent 101.

In an alternative embodiment, the distal end of the optical fiber 203may be fitted or fabricated with a means for selectively directing theUV light waves onto the inner surface 110 of the inner photodegradablelayer 103. As an example, FIG. 4 a shows a lens 400 which may be affixedto the distal tip of the fiber 203 for redirecting the UV light waves ina direction approximately normal to the longitudinal axis of the opticalfiber 203. Such a configuration may provide a larger fraction of UVwaves 425 propagating towards the top portion of the innerphotodegradable layer 103. In other words, the UV waves 425 areredirected in the direction of the surface of the lens 400. FIG. 4 bshows that the optical fiber 203 may be rotated so as to angle the lens400 downwards. Such a configuration may provide a larger fraction of UVwaves 426 propagating towards the bottom portion of the innerphotodegradable layer 103. Such selective redirecting of the UV wavesmay also be utilized when activating, degrading, and removing portionsof the outer photodegradable layer 102.

The distal end of the optical fibers 203 and/or 303 can have variousother attachments that will effect this purpose or alternatively theoptical fibers 203 and/or 303 themselves can be fabricated so that itside-fires at its end. For example, in addition to the lens surface 400described above in FIGS. 4 a and 4 b, the distal tip of the opticalfiber 203 and/or 303 can be made side-firing by beveling the end at anangle of approximately 45° and then applying a mirrored surface to thebeveled end. Another example of a side-firing end of the optical fiber203 and/or 303 can be made by creating a concave cone-shaped recesswithin the end of the optical fiber 203 and/or 303, and then applying amirrored surface to the concave surface. In addition to these examples,many other optical attachments and means of modifying the end of theoptical fiber 203 and/or 303 may be utilized as known in the art.Several other optical means that are well known to achieve thisredirection which involve reflection of a mirrored concave cone-shapedrecess, mirrored bevels, and defracting and refracting means may also beused.

Variations for removal of the inner photodegradable layer 103 and theouter photodegradable layer 102 are contemplated. For example, thesequence of removal of the inner and outer photodegradable layers 103and 102 are interchangeable such that the outer photodegradable layer102 may be removed before the inner photodegradable layer 103. Asanother example, only a portion of the inner and outer photodegradablelayers 103 and 102 may be activated, degraded, and removed.

Although the above described method shows both an inner and outerphotodegradable layers 103 and 102, the stent 100 may comprise a singleprotective layer. In particular, the stent 100 may comprise either aninner photodegradable layer 103 or an photodegradable layer 102.

Although optical fibers have been shown, other energy conducting meansas known in the art may be used to propagate and transmit the UV wavesfrom UV light source 271 to the photodegradable inner layer 103 and thephotodegradable outer layer 102.

Various biodegradable polymeric materials may be used to form stent 101.The biodegradable polymer may comprise a polylactic acid (PLA), whichmay be a mixture of enantiomers typically referred to as poly-D,L-lactic acid. PLA is one of the poly-α-hydroxy acids, which may bepolymerized from a lactic acid dimer. This polymer has two enantiomericforms, poly(L-lactic acid) (PLLA) and poly(D-lactic acid) (PDLA), whichdiffer from each other in their rate of biodegradation. PLLA issemicrystalline, whereas PDLA is amorphous, which may be desirable forapplications such as drug delivery where it is important to have ahomogeneous dispersion of an active species. PLA has excellentbiocompatibility and slow degradation, is generally more hydrophobicthan polyglycolic acids (PGA). The polymer used may also desirablycomprise polyglycolic acids (PGA). Polyglycolic acid is a simplealiphatic polyester that has a semi-crystalline structure, fullydegrades in 3 months, and undergoes complete strength loss by 1 month.Compared with PLA, PGA is a stronger acid and is more hydrophilic, and,thus, more susceptible to hydrolysis.

Other desirable biodegradable polymers for use include, but are notlimited to, polylactic glycolic acids (PLGA) and other copolymers of PLAand PGA. The properties of the copolymers can be controlled by varyingthe ratio of PLA to PGA. For example, copolymers with high PLA to PGAratios generally degrade slower than those with high PGA to PLA ratios.

Still other desirable polymers for use include poly(ethylene glycol)(PEG), polyanhydrides, polyorthoesters, fullerene,polytetrafluoroethylene, poly(styrene-b-isobutylene-b-styrene),polyethylene-co-vinylacetate, poly-N-butylmethacrylate, amino acid-basedpolymers (such as poly(ester) amide), SiC, TiNO, Parylene C, heparin,porphorylcholine.

A number of biodegradable homopolymers, copolymers, or blends ofbiodegradable polymers are known in the medical arts. These include, butare not limited to: polyethylene oxide (PEO), polydioxanone (PDS),polypropylene fumarate, poly(ethyl glutamate-co-glutamic acid),poly(tert-butyloxy-carbonylmethyl glutamate), polycaprolactones (PCL),polyhydroxybutyrates (PHBT), polyvalerolactones, polyhydroxyvalerates,poly(D,L-lactide-co-caprolactone) (PLA/PCL), polycaprolactone-glycolides(PGA/PCL), polyphosphate ester), and poly(hydroxy butyrate),polydepsipeptides, maleic anhydride copolymers, polyphosphazenes,polyiminocarbonates, polyhydroxymethacrylates, polytrimethylcarbonates,cyanoacrylate, polycyanoacrylates, hydroxypropylmethylcellulose,polysaccharides (such as hyaluronic acid, chitosan and regeneratecellulose), fibrin, casein, and proteins (such as gelatin and collagen),poly-e-decalactones, polylactonic acid, polyhydroxybutanoic acid,poly(1,4-dioxane-2,3-diones), poly(1,3-dioxane-2-ones),poly-p-dioxanones, poly-b-maleic acid, polycaprolactonebutylacrylates,multiblock polymers, polyether ester multiblock polymers,poly(DTE-co-DT-carbonate), poly(N-vinyl)-pyrrolidone, polyvinylalcohols,polyesteramides, glycolated polyesters, polyphosphoesters,poly[p-carboxyphenoxy)propane], polyhydroxypentanoic acid,polyethyleneoxide-propyleneoxide, polyurethanes, polyether esters suchas polyethyleneoxide, polyalkeneoxalates, lipides, carrageenanes,polyamino acids, synthetic polyamino acids, zein, polyhydroxyalkanoates,pectic acid, actinic acid, carboxymethylsulphate, albumin, hyaluronicacid, heparan sulphate, heparin, chondroitinesulphate, dextran,b-cyclodextrines, gummi arabicum, guar, collagen-N-hydroxysuccinimide,lipides, phospholipides, resilin, and modifications, copolymers, and/ormixtures of any of the carriers identified herein.

Other suitable biodegradable polymers that may be used include, but arenot limited to: aliphatic polyesters (including homopolymers andcopolymers of lactide), poly(lactide-co-glycolide),poly(hydroxybutyrate-co-valerate),poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV), polyoxaster andpolyoxaesters containing amido groups, polyamidoester, poly(glycolicacid-co-trimethylene carbonate), poly(trimethylene carbonate), andbiomolecules and blends thereof such as fibrinogen, starch, elastin,fatty acids (and esters thereof), glucoso-glycans, and modifications,copolymers, and/or mixtures or combinations of any of the carriersidentified herein.

The hybrid stent 100 may be created by coating the biodegradable stent101 in any way known in the art. As an example, the biodegradable stent101 may be extruded as known in the art. The inner photodegradable layer103 may be coated onto the inner surface 110, and the outerphotodegradable layer 102 may be coated onto the outer surface 111 ofthe extruded stent 101. Any means for coating as known in the art may beutilized, including dip coating or spray coating. Preferably, the stent101 is coated on a mandrel with the stent 101 in its expanded state orat least in its partially expanded state. Alternatively, otherstructural variations to the inner and outer photodegradable layers 103and 102 are contemplated. For example, stent 101 may be inserted into anouter photodegradable sleeve. An inner photodegradable sleeve may alsobe slid within the luminal space 104 of stent 101. Biodegradable suturesas known in the art (e.g., 3-0 or 4-0 polydiaxanone absorbablemonofilament sutures as commercially made and sold by Ethicon) may beutilized to affix the outer and the inner photodegradable sleeves.Alternatively, only an outer photodegradable sleeve may be used.Alternatively, the photodegradable layers 103 and 102 may be coextrudedwith the biodegradable layer 101.

In addition to the tubular main body shown in the Figures, thebiodegradable stent 101 may comprise any other stent architecture asknown in the art. In one example, the stent 101 may be braided on amandrel from any one of the above mentioned biodegradable materials. Inanother example, the stent 101 may be coiled. In still anotherembodiment, the tubular body may be formed entirely from thephotodegradable material described above. When the stent 100 is nolonger required (e.g., the condition causing the stricture or otherobstruction has been successfully resolved), degradation of theprotective photodegradable layers 102 and 103 can begin. UV lightcontacts the photodegradable layers 102 and 103, which causes thephotodegradable layers 102 and 103 to become activated and thereafterdegrade. Because the entire stent 100 is composed form thephotodegradable layers 102 and 103, the entire stent 101 isdisintegrated such that an additional biodegradation process does notoccur. Additionally, having the stent 100 formed entirely from aphotodegradable layer may be advantageous to disintegrate the innerphotodegradable layer that may have built-up encrustration thereon.Disintegration of the inner photodegradable layer exposes a cleansurface with no encrustration, which can extend the life of the stent100.

The biodegradable stent 101 may also be loaded with one or morebioactives in a therapeutically effective amount along at least aportion of the outer surface 111. As used herein, the term “bioactive”refers to any pharmaceutically active agent that produces an intendedtherapeutic effect on the body to treat or prevent conditions ordiseases. The bioactive may be loaded along any portion of stent 101.Preferably, the bioactive is loaded along the outer surface 111 ofbiodegradable stent 101. In such an embodiment, the outerphotodegradable layer 102 may serve as both the elution carrier and theprotective chemically inert layer. A “therapeutically-effective amount”as used herein is the minimal amount of a bioactive which is necessaryto impart therapeutic benefit to a human or veterinary patient. Forexample, a “therapeutically effective amount” to a human or veterinarypatient is such an amount which induces, ameliorates or otherwise causesan improvement in the pathological symptoms, disease progression orphysiological conditions associated with or resistance to succumbing toa disorder, for example restenosis. Accordingly, elution of thebioactive can occur when the protective outer photodegradable layer 102is degraded as described above with reference to FIGS. 3 a-3 c.

In one embodiment, the bioactive is an antithrombogenic agent. Devicescomprising an antithrombogenic agent are particularly preferred forimplantation in areas of the body that contact blood. Anantithrombogenic agent is any agent that inhibits or prevents thrombusformation within a body vessel. Types of antithrombotic agents includeanticoagulants, antiplatelets, and fibrinolytics. Examples ofantithrombotics include but are not limited to anticoagulants such asthrombin, Factor Xa, Factor VIIa and tissue factor inhibitors;antiplatelets such as glycoprotein IIb/IIIa, thromboxane A2, ADP-inducedglycoprotein IIb/IIIa, and phosphodiesterase inhibitors; andfibrinolytics such as plasminogen activators, thrombin activatablefibrinolysis inhibitor (TAFI) inhibitors, and other enzymes which cleavefibrin. Further examples of antithrombotic agents include anticoagulantssuch as heparin, low molecular weight heparin, covalent heparin,synthetic heparin salts, coumadin, bivalirudin (hirulog), hirudin,argatroban, ximelagatran, dabigatran, dabigatran etexilate,D-phenalanyl-L-poly-L-arginyl, chloromethy ketone, dalteparin,enoxaparin, nadroparin, danaparoid, vapiprost, dextran, dipyridamole,omega-3 fatty acids, vitronectin receptor antagonists, DX-9065a,CI-1083, JTV-803, razaxaban, BAY 59-7939, and LY-51,7717; antiplateletssuch as eftibatide, tirofiban, orbofiban, lotrafiban, abciximab,aspirin, ticlopidine, clopidogrel, cilostazol, dipyradimole;fibrinolytics such as alfimeprase, alteplase, anistreplase, reteplase,lanoteplase, monteplase, tenecteplase, urokinase, streptokinase, orphospholipid encapsulated microbubbles; and other bioactive agents suchas endothelial progenitor cells or endothelial cells.

Another example of an antithrombotic agent is a nitric oxide source suchas sodium nitroprussiate, nitroglycerin, S-nitroso and N-nitrosocompounds. In one embodiment, a material capable of releasing nitricoxide from blood-contacting surfaces can be delivered by the device ofthe invention.

Other examples of bioactive agents suitable for inclusion in the devicesof the present invention include antiproliferative/antimitotic agentsincluding natural products such as vinca alkaloids (vinblastine,vincristine, and vinorelbine), paclitaxel, rapamycin analogs,epidipodophyllotoxins (etoposide, teniposide), antibiotics (dactinomycin(actinomycin D) daunorubicin, doxorubicin and idarubicin),anthracyclines, mitoxantrone, bleomycins, plicamycin (mithramycin) andmitomycin, enzymes (for example, L-asparaginase which systemicallymetabolizes L-asparagine and deprives cells which do not have thecapacity to synthesize their own asparagine); antiplatelet agents suchas (GP) II.sub.b/III.sub.a inhibitors and vitronectin receptorantagonists; antiproliferative/antimitotic alkylating agents such asnitrogen mustards (mechlorethamine, cyclophosphamide and analogs,melphalan, chlorambucil), ethylenimines and methylmelamines(hexamethylmelamine and thiotepa), alkyl sulfonates-busulfan,nirtosoureas (carmustine (BCNU) and analogs, streptozocin),trazenes-dacarbazinine (DTIC); antiproliferative/antimitoticantimetabolites such as folic acid analogs (methotrexate), pyrimidineanalogs (fluorouracil, floxuridine, and cytarabine), purine analogs andrelated inhibitors (mercaptopurine, thioguanine, pentostatin and2-chlorodeoxyadenosine {cladribine}); platinum coordination complexes(cisplatin, carboplatin), procarbazine, hydroxyurea, mitotane,aminoglutethimide; hormones (i.e. estrogen); anticoagulants (heparin,synthetic heparin salts and other inhibitors of thrombin); fibrinolyticagents (such as tissue plasminogen activator, streptokinase andurokinase), aspirin, dipyridamole, ticlopidine, clopidogrel, abciximab;antimigratory; antisecretory (breveldin); anti-inflammatory: such asadrenocortical steroids (cortisol, cortisone, fludrocortisone,prednisone, prednisolone, 6.alpha.-methylprednisolone, triamcinolone,betamethasone, and dexamethasone), non-steroidal agents (salicylic acidderivatives i.e. aspirin; para-aminophenol derivatives i.e.acetaminophen; indole and indene acetic acids (indomethacin, sulindac,and etodalac), heteroaryl acetic acids (tolmetin, diclofenac, andketorolac), arylpropionic acids (ibuprofen and derivatives), anthranilicacids (mefenamic acid, and meclofenamic acid), enolic acids (piroxicam,tenoxicam, phenylbutazone, and oxyphenthatrazone), nabumetone, goldcompounds (auranofin, aurothioglucose, gold sodium thiomalate);immunosuppressives (cyclosporine, tacrolimus (FK-506), sirolimus(rapamycin), tacrolimus, everolimus, azathioprine, mycophenolatemofetil); angiogenic agents: vascular endothelial growth factor (VEGF),fibroblast growth factor (FGF); angiotensin receptor blockers; nitricoxide and nitric oxide donors; antisense oligionucleotides andcombinations thereof; cell cycle inhibitors, mTOR inhibitors, and growthfactor receptor signal transduction kinase inhibitors; retenoids;cyclin/CDK inhibitors; endothelial progenitor cells (EPC); angiopeptin;pimecrolimus; angiopeptin; HMG co-enzyme reductase inhibitors (statins);metalloproteinase inhibitors (batimastat); protease inhibitors;antibodies, such as EPC cell marker targets, CD34, CD133, and AC133/CD133; Liposomal Biphosphate Compounds (BPs), Chlodronate,Alendronate, Oxygen Free Radical scavengers such as Tempamine and PEA/NOpreserver compounds, and an inhibitor of matrix metalloproteinases,MMPI, such as Batimastat. Still other bioactive agents that can beincorporated in or coated on a frame include a PPAR .alpha.-agonist, aPPAR .delta. agonist and RXR agonists, as disclosed in published U.S.Patent Application US2004/0073297 to Rohde et al., published on Apr. 15,2004 and incorporated in its entirety herein by reference. In anotherembodiment, the bioactive is paclitaxel, rapamycin, a rapamycinderivative, an antisense oligonucleotide, or a mTOR.

The above mentioned hybrid stent 100 overcomes the problems associatedwith premature biodegradation of biodegradable stents by implementing aprotective outer photodegradable layer over a biodegradable stent. Byavoiding premature biodegradation, the stent 100 is able to exertsufficient radial strength at the target body lumen for the desired timeperiod. Accordingly, the patency of the body lumen is achieved. When thestent 100 is no longer needed, the photodegradable layers 102 and 103can be UV degraded so as to allow the stent body 101 to undergobiodegradation. The autonomous biodegradation advantageously eliminatesan additional procedure typically required for removing the stent 101.

While preferred embodiments of the invention have been described, itshould be understood that the invention is not so limited, andmodifications may be made without departing from the invention. Thescope of the invention is defined by the appended claims, and alldevices that come within the meaning of the claims, either literally orby equivalence, are intended to be embraced therein. Furthermore, theadvantages described above are not necessarily the only advantages ofthe invention, and it is not necessarily expected that all of thedescribed advantages will be achieved with every embodiment of theinvention.

1. A hybrid degradable stent comprising: a generally tubular main bodycomprising an inner diameter and an outer diameter, wherein the tubularbody is formed from a biodegradable material; and a photodegradablelayer disposed over at least a portion of the inner diameter and/or theouter diameter of the biodegradable tubular body, wherein the layer isformed from a photodegradable material that is chemically inert tobodily fluids contained at an implanted site, the photodegradable layerselectively adapted to be activated from a chemically inert state to aphotodegradable state, wherein the photodegradable state initiatesdegradation of the photodegradable layer so as to expose at least aportion of the biodegradable material to begin biodegradation of thebiodegradable material.
 2. The hybrid degradable stent of claim 1,wherein the photodegradable layer is selectively adapted to be activatedfrom the chemically inert state to the photodegradable state by aultraviolet (UV) light-irradiating system.
 3. The hybrid degradablestent of claim 2, wherein the light-irradiating system comprises aultraviolet (UV) light source and an optical fiber section, the fibersection comprising a proximal section in communication with the UV lightsource and a distal section in communication with the inner diameterand/or the outer diameter of the tubular body, wherein the fiber sectionis adapted to propagate and transmit UV light from the proximal sectionto the distal section, and thereafter irradiate light from the distalsection to the tubular body.
 4. The hybrid degradable stent of claim 1,wherein the photodegradable material comprises a UV photodegradableketocarbonyl containing polymer.
 5. The hybrid degradable stent of claim3, wherein the optical fiber comprises a lens surface for redirectingthe UV light.
 6. The hybrid degradable stent of claim 4, wherein thephotodegradable material further comprises a synthetic polymer formedfrom a vinylidene monomer.
 7. The hybrid degradable stent of claim 6,wherein the photodegradable ketocarbonyl comprises a chemicalcomposition ranging from about 0.01 wt % to about 5 wt %, based upon thetotal weight of the synthetic polymer
 8. The hybrid degradable stent ofclaim 1, wherein the biodegradable tubular main body comprises abioactive loaded therewithin.
 9. The hybrid degradable stent of claim 1,wherein the photodegradable layer is nonporous and extends along anentire length of the inner diameter and the outer diameter of thebiodegradable tubular main body.
 10. A degradable stent kit comprising:a generally biodegradable tubular body comprising a proximal end and adistal end, and a lumen extending from the proximal end to the distalend, the body further comprising a photodegradable material disposedover at least a portion of the biodegradable tubular body that ischemically inert when deployed into a body lumen of a patient; and alight-irradiating system configured to activate the photodegradablematerial from the chemically inert state to a photodegradable state, thelight-irradiating system comprising a light source and a fiber section,the fiber section comprising a proximal section in communication withthe light source and a distal section in communication with the tubularbody, wherein the fiber section is adapted to propagate UV light fromthe proximal section to the distal section and thereafter irradiate UVlight from the distal section to the photodegradable material.
 11. Thekit of claim 10, wherein the fiber section is an optical fiber.
 12. Thekit of claim 10, wherein the light-irradiating system further comprisesan intensity control to regulate the amount of UV light to be deliveredto the optical fiber.
 13. The kit of claim 10, wherein the tubular bodyis formed entirely from the photodegradable material.
 14. The kit ofclaim 10, wherein the light-irradiating system further comprises awavelength tuning control for selecting UV light of a suitablewavelength to interact with the photodegradable material.
 15. The kit ofclaim 10, wherein the optical fiber comprises a means for selectivelydirecting the UV light waves onto the photodegradable material.
 16. Thekit of claim 10, wherein the photodegradable layer is disposed over theentire tubular body.
 17. A method for controllably degrading a stentwithin a body lumen of a patient, comprising the steps of: (a) providinga generally tubular body formed from a biodegradable material, the bodycomprising an inner diameter and an outer diameter, the body furthercomprising a photodegradable layer disposed over at least a portion ofthe inner and/or the outer diameters of the biodegradable tubular body;(b) deploying the tubular body into the body lumen; (c) advancing anelongated light-irradiating conductor towards the deployed tubular body;(d) irradiating a specific wavelength of light along the conductor andtowards the photodegradable layer of the stent; (e) activating thephotodegradable layer from a chemically inert state to a photodegradablestate; and (f) photodegrading at least a portion of the photodegradablelayer.
 18. The method of claim 17, further comprising the step ofphotodegrading the photodegradable layer a sufficient amount so as toexpose at least a portion of the biodegradable tubular body.
 19. Themethod of claim 18, further comprising the step of biodegrading theexposed biodegradable tubular body.
 20. The method of claim 19, furthercomprising the step of providing a bioactive along the biodegradabletubular body and eluting the bioactive.